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Alternative synthesis of six-membered oxygen-heterocycles was demonstrated in examples of chroman and pyranoquinone, which constitute a large class of biologically active natural products. Here, allenyl and alkynyl groups were utilized as the substituents at the 4-position. An approach to chroman depends on combination of the 4n-6n electrocyclic reactions and an intramolecular hetero Diels-Alder reaction [87]. The prerequisite structure was constructed by introduction of a designed alkyne 67 to 5 (R = Me) followed by F--promoted isomerization to the allenyl function at C-4 (68 ^ 69). The key thermal reactions (50 °C, 36 h) involving both electrocyclic ring opening of 69 and consecutive intramolecular [4 + 2] cycloaddition of o-quinone methide 70 afforded the hexahydrocannabinol analog 71 (Scheme 12).

In the case of an alkynyl substituent, the targeted pyranoquinone 76 was obtained by thermolysis (toluene reflux 1.5 h) of the adduct 72 prepared

from lithiated alkynyl glycopyranoside and 5 (R = Me), involving a more complicated route (Scheme 13). The rearrangements featuring the alkynyl substituent were envisaged to proceed via the mechanism in which ketene 73 and diradical intermediates 74 and 75 participate. The electrocyclization was succeeded by 6-exo radical cyclization and H-abstraction to lead to the quinone ring [88]. Interestingly, it was pointed out that such diradical intermediates formed during thermolysis of 4-alkynylcyclobutenones contributed

Scheme 13 Synthesis of pyranoquinone by 4n-6n electrocyclic reactions followed by cyclization of the diradical intermediate [88,89]

DNA cleavage (mimic of esperamicin) [89]. The related diradical mechanism was operated in the photoannulation reaction of 2-aryl-3-isopropoxy-1,4-naphthoquinone available from 5 (R = i-Pr) and was fruitful in synthesis of dimethylnaphthogeranine E [90].

Furaquinocins are a class of antibiotics composed of naphthoquinone fused with an angular five-membered oxygen ring bearing the isoprenoid side chain. After the enantio- and diastereoselective construction of di-hydrobenzofuran and introduction of an unsaturated side chain via the Horner-Wadsworth-Emmons reaction, assembly of the naphthoquinone was achieved by the squaric acid based technology (addition of designed organolithium 78 to 77a/hydrolysis/heating of 79a at 110 °C/air oxida-tion/desilylation) to give furaquinocin E (80a). Different substitution patterns for biological testing were performed by changing those of squaric acid; the regioisomer (80b) of natural product E was accomplished by reversing the chemoselectivity from imine (i.e., 77a) to pristine carbonyl group (i.e., 77b) and structural isomers (80c, 80d) by placing the same substituents [91] (Scheme 14).